Adults 18 to 55, any sex, with Healthy Subjects or Pharmacokinetics. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Baseline-adjusted Area Under Effect Curve (AUEC) for LDL-C for Evolocumab and AlirocumabPrimary· Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
The values and variability of AUEC for LDL-C at low, intermediate-low, intermediate-high, and high doses of evolocumab and alirocumab. AUEC was calculated as the baseline-subtracted area under the LDL-C concentration-time curve expressed in units of mg/(dL\*day). More negative AUEC values represent greater reductions in LDL-C exposure from baseline. The standard deviation is noted in parentheses. For each subject and dose, the maximum decrease from baseline LDL-C was determined using all sampled timepoints. AUEC values were log-transformed and an ANCOVA model was used to calculate geometric me
Group
Value
95% CI
Arm A: Evolocumab Low Dose
-380
± 228
Arm B: Evolocumab Intermediate Low Dose
-754
± 573
Arm C: Evolocumab Intermediate High Dose
-866
± 658
Arm D: Evolocumab High Dose
-1832
± 806
Arm E: Alirocumab Low Dose
-580
± 360
Arm F: Alirocumab Intermediate Low Dose
-581
± 319
Arm G: Alirocumab Intermediate High Dose
-668
± 828
Arm H: Alirocumab High Dose
-1902
± 361
Arm I: Placebo
-350
± 881
Maximum Change From Baseline for LDL-C for Evolocumab and AlirocumabPrimary· Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
The values and variability of maximum change from baseline for LDL-C at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab
Group
Value
95% CI
Arm A: Evolocumab Low Dose
-27.7
± 11.8
Arm B: Evolocumab Intermediate Low Dose
-45.1
± 26.9
Arm C: Evolocumab Intermediate High Dose
-49.9
± 26.2
Arm D: Evolocumab High Dose
-70.1
± 25.0
Arm E: Alirocumab Low Dose
-35.8
± 16.3
Arm F: Alirocumab Intermediate Low Dose
-40.6
± 8.1
Arm G: Alirocumab Intermediate High Dose
-47.9
± 18.8
Arm H: Alirocumab High Dose
-54.6
± 12.1
Arm I: Placebo
-30.1
± 18.7
Baseline-adjusted AUEC for Apolipoprotein B (ApoB) for Evolocumab and AlirocumabSecondary· Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
The values and variability of AUEC for ApoB at low, intermediate-low, intermediate-high, and high doses of evolocumab and alirocumab. AUEC was calculated as the baseline-subtracted area under the ApoB concentration-time curve expressed in units of mg/(dL\*day). More negative AUEC values represent greater reductions in ApoB exposure from baseline. The standard deviation is noted in parentheses. For each subject and dose, the maximum decrease from baseline ApoB was determined using all sampled timepoints. AUEC values were log-transformed and an ANCOVA model was used to calculate geometric means
Group
Value
95% CI
Arm A: Evolocumab Low Dose
-207
± 313
Arm B: Evolocumab Intermediate Low Dose
-482
± 434
Arm C: Evolocumab Intermediate High Dose
-676
± 453
Arm D: Evolocumab High Dose
-1094
± 952
Arm E: Alirocumab Low Dose
-469
± 290
Arm F: Alirocumab Intermediate Low Dose
-462
± 231
Arm G: Alirocumab Intermediate High Dose
-128
± 536
Arm H: Alirocumab High Dose
-1087
± 707
Arm I: Placebo
-428
± 560
Maximum Change From Baseline for apoB for Evolocumab and AlirocumabSecondary· Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
The values and variability of maximal difference at a single time-point for ApoB at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab
Group
Value
95% CI
Arm A: Evolocumab Low Dose
24
± 12
Arm B: Evolocumab Intermediate Low Dose
32
± 17
Arm C: Evolocumab Intermediate High Dose
36
± 15
Arm D: Evolocumab High Dose
46
± 16
Arm E: Alirocumab Low Dose
23
± 9
Arm F: Alirocumab Intermediate Low Dose
29
± 6
Arm G: Alirocumab Intermediate High Dose
28
± 8
Arm H: Alirocumab High Dose
37
± 7
Arm I: Placebo
17
± 7
Maximum Concentration (Cmax) for Evolocumab and AlirocumabSecondary· 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8,12, 24, hours post-dose; once on Day 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
The values and variability of Cmax at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab
Group
Value
95% CI
Arm A: Evolocumab Low Dose
0.7
± 28
Arm B: Evolocumab Intermediate Low Dose
0.5
± 62
Arm C: Evolocumab Intermediate High Dose
2.0
± 54
Arm D: Evolocumab High Dose
6.2
± 36
Arm E: Alirocumab Low Dose
0.8
± 27
Arm F: Alirocumab Intermediate Low Dose
1.7
± 73
Arm G: Alirocumab Intermediate High Dose
2.9
± 61
Arm H: Alirocumab High Dose
6.9
± 41
Area Under the Curve (AUC) for Evolocumab and AlirocumabSecondary· 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8,12, 24, hours post-dose; once on Day 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
The values and variability of AUC at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab
Group
Value
95% CI
Arm A: Evolocumab Low Dose
2.4
± 67
Arm B: Evolocumab Intermediate Low Dose
0.8
± 91
Arm C: Evolocumab Intermediate High Dose
12.9
± 71
Arm D: Evolocumab High Dose
65.7
± 57
Arm E: Alirocumab Low Dose
8.3
± 55
Arm F: Alirocumab Intermediate Low Dose
17.1
± 57
Arm G: Alirocumab Intermediate High Dose
38.5
± 92
Arm H: Alirocumab High Dose
107.9
± 58
Dose-response Parameters (Slope) for LDL-C Area Under the Effect Curve Models for Evolocumab and AlirocumabSecondary· Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Model parameter (slope) for LDL-C area under the effect curve model: Mean slope value calculated after combining data from low, intermediate low, intermediate high, and high doses of evolocumab or alirocumab with placebo data. The units of measure for slope are mg/dL•day / (mg dose).
Group
Value
95% CI
Evolocumab: Area Under the Effect Curve Model for LDL-C
-11
-15 – -6
Alirocumab: Area Under the Effect Curve Model for LDL-C
-15
-21 – -9
Pharmacodynamic Model Parameter, Maximum Effect (Emax), for LDL-C Maximum Change From Baseline Models With Evolocumab and AlirocumabSecondary· Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Model parameter (Emax) for LDL-C maximum change from baseline curve models calculated after combining data from low, intermediate low, intermediate high, and high doses of evolocumab or alirocumab with placebo data.
Group
Value
95% CI
Evolocumab: Maximum Change From Baseline Model for LDL-C
84
55 – 113
Alirocumab: Maximum Change From Baseline Model for LDL-C
62
50 – 75
Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for LDL-C Maximum Change From Baseline Models With Evolocumab and AlirocumabSecondary· Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Model parameter (ED50) for LDL-C maximum change from baseline curve models calculated after combining data from low, intermediate low, intermediate high, and high doses of evolocumab or alirocumab with placebo data.
Group
Value
95% CI
Evolocumab: Maximum Change From Baseline Model for LDL-C
32
0 – 66
Alirocumab: Maximum Change From Baseline Model for LDL-C
14
5 – 23
Adverse events — posted to ClinicalTrials.gov
Time frame: 42 days for subjects in treatment groups A, B, E, and F; 56 days for subjects in treatment groups C and G; and 84 days for subjects in treatment groups D, H, and I.
Reporting threshold: 0%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
This study is designed to assess pharmacokinetics and pharmacodynamics of evolocumab and alirocumab across an appropriate dose range to inform clinical trial operating characteristics for future clinical pharmacology pharmacodynamics similarity studies.
This is a randomized, placebo-controlled, single-dose, parallel arm study in 72 healthy subjects assigned to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (evolocumab and alirocumab ) or placebo.
Publications & conference data
No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.
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Sponsor: as reported to ClinicalTrials.gov by Food and Drug Administration (FDA)
Last refreshed: 22 April 2024
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04189484.